학술논문
Recruitment of plasma cells from IL-21-dependent and IL-21-independent immune reactions to the bone marrow
Document Type
article
Author
Marta Ferreira-Gomes; Yidan Chen; Pawel Durek; Hector Rincon-Arevalo; Frederik Heinrich; Laura Bauer; Franziska Szelinski; Gabriela Maria Guerra; Ana-Luisa Stefanski; Antonia Niedobitek; Annika Wiedemann; Marina Bondareva; Jacob Ritter; Katrin Lehmann; Sebastian Hardt; Christian Hipfl; Sascha Hein; Eberhard Hildt; Mareen Matz; Henrik E. Mei; Qingyu Cheng; Van Duc Dang; Mario Witkowski; Andreia C. Lino; Andrey Kruglov; Fritz Melchers; Carsten Perka; Eva V. Schrezenmeier; Andreas Hutloff; Andreas Radbruch; Thomas Dörner; Mir-Farzin Mashreghi
Source
Nature Communications, Vol 15, Iss 1, Pp 1-16 (2024)
Subject
Language
English
ISSN
2041-1723
Abstract
Abstract Bone marrow plasma cells (BMPC) are the correlate of humoral immunity, consistently releasing antibodies into the bloodstream. It remains unclear if BMPC reflect different activation environments or maturation of their precursors. Here we define human BMPC heterogeneity and track the recruitment of antibody-secreting cells (ASC) from SARS-CoV-2 vaccine immune reactions to the bone marrow (BM). Trajectories based on single-cell transcriptomes and repertoires of peripheral and BM ASC reveal sequential colonisation of BMPC compartments. In activated B cells, IL-21 suppresses CD19 expression, indicating that CD19low-BMPC are derived from follicular, while CD19high-BMPC originate from extrafollicular immune reactions. In primary immune reactions, both CD19low- and CD19high-BMPC compartments are populated. In secondary immune reactions, most BMPC are recruited to CD19high-BMPC compartments, reflecting their origin from extrafollicular reactivations of memory B cells. A pattern also observable in vaccinated-convalescent individuals and upon diphtheria/tetanus/pertussis recall-vaccination. Thus, BMPC diversity reflects the evolution of a given humoral immune response.